Human Genetics & Inheritance

Chromosomes are the cellular carriers of genes and are the functional unit of heredity. First described by Mendel in 1865, each gene can exist in an array of different forms called alleles. Hereditary traits are passed to offspring through alleles each given by the parents. The distribution of homologous chromosomes during meiosis, of which one of each pair is randomly chosen, is conveyed to each haploid cell. Genes are passed to the offspring, and each time that the genome is replicated, transcribed, and translated, proteins that reflect the combination of hereditary traits is reflected in the phenotype.

Autosomal Inheritance

Autosomal inheritance is a pattern of inheritance in which the transmission of traits depends on the presence of absence of certain alleles on the alleles. This pattern may be dominant or recessive.

The appearance or physical structure of an individual is referred to as its phenotype and the genetic composition as its genotype. Individuals with identical phenotypes may possess different genotypes, so to determine the genotype; it is necessary to perform a genetic cross for several generations. Homozygous refers to a gene pair in which both the maternal and paternal genes are identical. In contrast, gene pairs in which paternal genes are different from the maternal genes are called heterozygous.

When all of the offspring of the F1 generation have the phenotype of one parent, it is suspected that the gene was inherited on a dominant allele. Traits that do not appear in the F1 generation of progeny are might, therefore, said to be recessive. Mendel was able to set up genetic crosses between F1 offspring, which gave important results.

In 25 % of the F2 generation, the recessive trait was displayed; and the dominant trait was displayed in 75 % of these offspring. For traits that are of autosomal dominant inheritance pattern, the ratio in F2 of dominant to recessive traits will always be 3:1.

One of the several letters may be used to represent a given gene. The dominant allele of the gene is indicated by a capital letter, by a superscript, or by a +. A recessive allele is indicated by a lowercase letter. A given gamete contains only one of the two copies of the genes present in the parent it comes from, for example, either G or g, but never both.

The two types of gametes are produced in equal numbers so there is a 50:50 chance that a given gamete will contain the particular gene (G or g), and the choice is purely random. You would not expect to find exact 3:1 ratios when we examine a limited number of F2 offspring. The ratio will sometimes be slightly higher and other times slightly lower. But as you look at increasingly larger samples, you should expect that the ratio of offspring with the dominant trait to offspring with the recessive trait will approximate the 3:1 ratio more and more closely.

Mendelian laws

The Mendelian fashion of inheritance is guided by the three Mendelian laws which can be summarized by a statement. Genes come in pairs that are inherited independently and each deduced from each parent. Thus, the laws include:

This law of segregation is frequently referred to as Mendel’s first law. It states that traits are inherited in pairs for the trait to be carried down in the same format to the offspring separation into one trait happens in the parent for each sex cell. The reappearance of the recessive characteristic in the F2 generation indicates that recessive alleles are neither modified nor lost in the Fl (Gg) generation, but that the dominant and recessive genes are independently transmitted and so can segregate independently during the formation of sex cells.

Mendel’s second law, the law of Independent Assortment, explains offspring that differ by more than one characteristic. These characteristics are individually carried down to the offspring independent of other traits. To demonstrate this, Mendel bred two strains of peas. One of the strains had round yellow seeds; the other, wrinkled green seeds. Since round and yellow are dominant over wrinkled and green, the entire Fl generation produced round yellow seeds.

“Linking Mendel and Chromosomes. During Meisosis chromosomes undergo segregation and independent assortment” Image created by Lecturio

The Fl generation was then crossed within itself to produce some F2 progeny, which were examined for seed appearance (phenotype). In addition to the two original phenotypes (round yellow; wrinkled green), two new types (recombinants) emerged: wrinkled yellow and round green.

Again Mendel found he could interpret the results by the postulate of genes if he assumed that each gene pair was independently transmitted to the gamete during sex-cell formation. Anyone gamete contains only one type of allele from each gene pair. Thus, the gametes produced by a Fl (RrYy) will have the composition RY, Ry, rY, or ry, but never Rr, Yy, YY, or RR. Furthermore, in this example, all four possible gametes are produced with equal frequency. There is no tendency of genes arising from one parent to stay together.

As a result, the F2 progeny phenotypes appear in the ratio nine round yellow, three round green, three wrinkled yellow, and one wrinkled green as depicted in a Punnett square.

Further, this idea can be extrapolated to the Chromosomal Theory of Heredity, because the yellow- and green-seed genes are carried on a certain pair of chromosomes and that the round- and wrinkled-seed genes are carried on a different pair. This hypothesis immediately explains the experimentally observed 9:3:3:1 segregation ratios.

Mendel’s principle of independent assortment is based on the fact that genes located on different chromosomes behave independently during meiosis. Often, however, two genes do not assort independently because they are located on the same chromosome. This linkage is never complete, and the probability that two genes on the same chromosome will remain together during meiosis ranges from just less than 100% to nearly 50%. This variation in linkage suggests that there must be a mechanism for exchanging genes on homologous chromosomes. This mechanism is called crossing over.

At the start of meiosis, through the process of synapsis, the homologous chromosomes form pairs with their long axes parallel. At this stage, each chromosome has duplicated to form two chromatids. Thus, synapsis brings together four chromatids (a tetrad), which coil about one another. Because of tension resulting from this coiling, two of the chromatids might sometimes break at a corresponding place on each. These events could create four broken ends, which might rejoin crossways so that a section of each of the two chromatids would be joined to a section of the other.

In this manner, recombinant chromatids produced contain segments derived from each of the original homologous chromosomes.

Genes are normally copied exactly during chromosome duplication. Rarely, however, changes (mutations) occur in genes to give rise to altered forms, most—but not all—of which function less well than the wild-type alleles. This process is necessarily rare; otherwise, many genes would be changed during every cell cycle, and offspring would not ordinarily resemble their parents. There is, instead, a strong advantage in there being a small but finite mutation rate; it provides a constant source of new variability, necessary to allow plants and animals to adapt to a constantly changing physical and biological environment.

From the above the third law of mendelian inheritance can be deduced as follows in cases where there are alternative forms of a gene, then the dominant gene is expressed. This is known as the law of dominance.

X & Y Chromosomes

In the XY chromosome system, females possess two chromosomes of the same kind (XX), and males have (XY) chromosomes. In humans, a single gene called SRY signals the developmental pathway towards maleness. There are exceptions to this rule, where XX males or XY females develop (android insensitivity syndrome). Another example is Turner’s syndrome, where a single X chromosome is present. Additionally, for example in Klinefelter’s syndrome, there are two XX chromosomes and a Y chromosome present XYY or XXYY syndrome.

Modes of Inheritance

There are different modes of inheritance, such as autosomal dominant, autosomal recessive, X-linked dominant, X-linked recessive, and mitochondrial.

In autosomal dominant inheritance, one copy of a disease allele is sufficient for an individual to be susceptible to expressing the disease in their phenotype. The offspring have a 50 % chance of inheriting the diseased allele. Across a population, males and females should display the disease in equal frequencies. Myotonic muscular dystrophy and Huntington’s disease are examples of autosomal dominant disorders.

Autosomal recessive disorders, such as sickle-cell anemia and cystic fibrosis, require two copies of the disease allele for an individual to be susceptible to express the disease. A one in four (25 %) chance exists that the children will inherit the disease; 50 % chance that the child will be a carrier, and 25 % chance that the child will carry no copies of the disease. Like autosomal dominant inheritance, the distribution of male-to-female inheritance will be equal.

X-linked inherited diseases, such as oral-facial-digital syndrome type I, hypophosphatemia rickets, fragile X syndrome, require one copy of the disease allele. Males and females alike can be affected, although males are usually more severely affected because they carry only one copy of the genes that are found on the X chromosome. Additionally, there are X-linked disorders that are lethal in males. When an X-linked disease affects a female, 50% of her offspring have susceptibility for inheriting the disease. In the case of a male, all of his daughters will be affected, but none of his sons will.

Blood types

In blood type inheritance, each biological parent will donate one of their two ABO alleles to their offspring. A mother who is type O can only pass an O allele to her child, and a father who is AB-type can pass either an A or B to his child. This couple could have a child of either blood type A (O from mom and A from dad) or type B (O from mom and B from dad).

Since there are four different maternal blood types and four different paternal types possible, there are 16 different combinations (44) possible for their offspring.

The Rh factor is also inherited but is independent of the ABO blood type alleles. There are two different alleles for Rh factor known as Rh+ and Rh-. Someone who is Rh+ has at least one Rh+ allele, but could have two. Their genotype is either Rh+/Rh+ or Rh+/Rh-. Someone who is Rh- has the genotype of Rh-/Rh-.

Like ABO alleles, each parent donates one of their two alleles to their offspring. A mother that is Rh- can only pass Rh- alleles to offspring and a father who is Rh+ can pass Rh+ or Rh-. This couple would have Rh+ (Rh- from mom and Rh+ from dad) or Rh- children (Rh- from mom and Rh- from dad).

Genomic Imprinting

Genomic imprinting is a mechanism by which certain genes are expressed in a specific manner, parent of origin-wise. In this case, an allele inherited from the father is imprinted, silenced, and only the allele from the mother is expressed.

Genomic imprinting is caused by DNA methylation, histone methylation, and effective processes under the umbrella of “Epigenetics”, that don’t alter the genetic sequence but instead silence them by making them unavailable to the transcription machinery. Examples of diseases that are susceptible to genomic imprinting are Angelman syndrome and Prader-Willi syndrome.

Review Questions

The correct answers can be found below the references.

1. A couple with normal color vision has eleven children, six males, and five females. Two of the boys are red-green colorblind, and all five of the girls have normal color vision. What mode of inheritance could this possibly be?

Sex-linked, because the males can only inherit their X chromosomes from their mother. The only way for a male to inherit red-green colorblindness is when the mother provides the allele in her gamete.

Autosomal dominant, the fact that only the males are color blind is purely a coincidence.

Autosomal recessive. The fact that females have a normal color vision is explained by Mendel’s First Law of Independent Assortment.

None of the above are possible explanations as to this case of inheritance.

2. Which of the following is a true statement regarding the ABO blood system?

People who are type AB produce both anti-A and anti-B antibodies.

The only ABO type blood that does not have either A or B antigens is the AB type.

Those who have the A antigen normally do not produce anti-A antibodies.

Those who have the A antigen normal produce anti-A antibodies.

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